Tag Archives: C. difficile research community

C. difficile Researcher Kirk Hevener Of ISU And Research Group At Texas A&M University and University of Hawaii Work On A New Way To Treat Clostridium difficile

Kirk Hevener of the ISU Department of Biomedical and Pharmaceutical Sciences is part of a group that is working on a new way to treat Clostridium difficile, commonly called
C. difficile or C. diff. Working with researchers from Texas A&M University and the University of Hawaii
, Hevener is researching a new target that could change the way C. diff is treated through a $415,000 grant from the National Institute of Health.

C. diff  is a bacteria that commonly causes infection of the colon and can lead to severe damage, and in some cases can even be fatal. It is also highly drug-resistant and extremely transmittable.

Hevener identified C. diff as a possible candidate for research while working with a completely different bacteria during his postdoctoral fellowship in Chicago.

Porphyromonas gingivalis is a bacteria that causes disease in the mouth.

While these two bacteria are unrelated, they have two common traits. Both are pathogenic, meaning they cause disease, and contain an enzyme called FabK.

FabK is not found in many other bacteria, so Hevener decided that C. diff would be a good candidate to extend his work in Chicago to, with FabK being the focus of his current work.

This enzyme is part of the fatty acid synthesis pathway. This creates lipids that are used to create the cell membrane, among other functions of the cell. Within C. diff, it is also is part of the mechanism that creates the bacteria’s spores. These spores are inactive forms of the bacteria and are extremely difficult to kill.  They are the reason that recurrence and transmission rates are so high inside of hospitals.

Hevener is studying ways this enzyme can be targeted specifically, with molecules known as inhibitors.

If he and his team can prove that FabK is targetable, it could lead to the development of new medications specific to the treatment of C. diff.

Hevener wanted to make clear that he is currently working on target validation, and not drug development. He and his team are validating that by inhibiting this enzyme, the bacteria would not be able to able to reproduce and create spores, which would then allow others to develop a medication to leverage this mechanism.

By targeting FabK specifically, Hevener’s team would create a narrow spectrum method of treatment, as opposed to the more common broad spectrum approach.

Broad spectrum antibiotics affect all bacteria, regardless if they are pathogenic or beneficial.

There are many bacteria found inside of the human body that aid in different ways from digestion to preventing harmful organisms causing infection.

This narrow spectrum approach has two benefits for a medication developed using it: it does not kill helpful organisms and it helps slow the development of resistance.

Hevener explained that it is impossible to create an antibiotic that is immune to the development of resistance, but because a medication of this type would affect only C. diff, other bacteria would not develop resistance and transfer that genetic mutation to other bacteria. This would slow the progress of a medication becoming less effective or possibly obsolete over time.

To read article in its entirety please click on the following link:

http://isubengal.com/narrowing-c-difficile/

Belgian Nursing Home Survey of Clostridium difficile Presence and Gut Microbiota Composition

  • Cristina Rodriguez+
  • Bernard Taminiau,
  • Nicolas Korsak,
  • Véronique Avesani,
  • Johan Van Broeck,
  • Philippe Brach,
  • Michel Delmée and
  • Georges Daube
Contributed equally
BMC MicrobiologyBMC series – open, inclusive and trusted201616:229

DOI: 10.1186/s12866-016-0848-7

The Author(s). 2016m,Received: 13 April 2016,Accepted: 23 September 2016

Published: 1 October 2016

Abstract

Background

Increasing age, several co-morbidities, environmental contamination, antibiotic exposure and other intestinal perturbations appear to be the greatest risk factors for C. difficile infection (CDI). Therefore, elderly care home residents are considered particularly vulnerable to the infection. The main objective of this study was to evaluate and follow the prevalence of C. difficile in 23 elderly care home residents weekly during a 4-month period. A C. difficile microbiological detection scheme was performed along with an overall microbial biodiversity study of the faeces content by 16S rRNA gene analysis.

Results

Seven out of 23 (30.4 %) residents were (at least one week) positive for C. difficile. C. difficile was detected in 14 out of 30 diarrhoeal samples (43.7 %). The most common PCR-ribotype identified was 027. MLVA showed that there was a clonal dissemination of C. difficile strains within the nursing home residents. 16S-profiling analyses revealed that each resident has his own bacterial imprint, which was stable during the entire study. Significant changes were observed in C. difficile positive individuals in the relative abundance of a few bacterial populations, including Lachnospiraceae and Verrucomicrobiaceae. A decrease of Akkermansia in positive subjects to the bacterium was repeatedly found.

Conclusions

A high C. difficile colonisation in nursing home residents was found, with a predominance of the hypervirulent PCR-ribotype 027. Positive C. difficile status is not associated with microbiota richness or biodiversity reduction in this study. The link between Akkermansia, gut inflammation and C. difficile colonisation merits further investigations.

Keywords

C. difficile Elderly care home residents 16S rRNA gene analysis

Background

Clostridium difficile is a Gram-positive, anaerobic, spore-forming, rod-shaped bacterium that has been widely described in the intestinal tract of humans and animals. In 1978, C. difficile was recognized as a major cause of antibiotic associated diarrhoea and, in the most serious cases pseudomembranous colitis [1, 2, 3]. Since then, many outbreaks have been reported; most of them were associated with the emergence of a specific subtype, hyper-virulent PCR-ribotype 027 [4]. Nowadays, C. difficile is a worldwide public health concern as it is considered the major cause of antibiotic-associated infections in healthcare settings [5]. A recent report of C. difficile infection (CDI) cost-of-illness attributes a mean cost ranging from 8,911 to 30,049 USD for hospitalised patients (per patient/admission/episode/infection) in the USA [6] and annual economic burden estimated around 3,000 million euro in Europe [7].

CDI is more commonly diagnosed among older people in nursing homes. High isolation frequencies have been described in USA, with up to 46 % of elderly residents testing positive for C. difficile, while in Europe or Canada the reported rates are much lower, varying between 0.8 and 10 % [8]. This is partly because elderly people are more commonly in hospitals, have an antibiotic treatment and age-related changes in intestinal flora and host defences, as well as the presence or other underlying health problem [8, 9, 10]. These factors can have an impact on the intestinal microbiota, which may promote C. difficile colonisation and the development of the infection [11]. Therefore, a new concern of several studies has been the identification of the microbial communities implicated in the CDI through the use of new sequencing techniques, like metagenomics [12].

The aim of this study was to evaluate and follow the prevalence of C. difficile among the residents of a Belgian nursing home. Multilocus variable number of tandem repeats analysis (MLVA) was performed to determine the genetic diversity of the C. difficile isolates and possible cross-infection between patients. Additionally, 16S rRNA gene sequencing was used to characterise the faecal microbiota of the elderly residents, to evaluate the global evolutions of the total microbiota and to identify possible relationships between certain bacteria populations and C. difficile colonisation, diarrhoea and antibiotic treatment.

Results

Prevalence of C. difficile

A total of 242 faecal samples were collected from 23 residents in seventeen consecutive weeks (resident number 11 was excluded from the study as he finally did not agree to participate in the survey). Two subjects passed away within the four-month study period. Seven out of 23 monitored residents were positive for C. difficile at least once (Table 1).
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University of Leicester Researchers Identified the Potential Of Using A Bacteriophage Cocktail To Eradicate C. difficile Infection (CDI)

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University of Leicester scientists have previously identified the potential of using a bacteriophage cocktail to eradicate Clostridium difficile infection (CDI)

 

and in this research, using an insect model, they show that their prophylactic use can prevent infection forming in the first place.

The data, which is the result of research conducted by University of Leicester researchers Dr. Janet Nale, and Professor Martha Clokie, both from the Department of Infection, Immunity and Inflammation, demonstrated that C. difficile phages are particularly effective when used to prevent infection, but they are also good at targeting harmful bacterial infections once biofilms have formed.

Using biofilm and waxworms as models, these phages reduced C. difficile bacterial counts when administered as a preventative measure. Furthermore, combinations of phages and vancomycin led to a marked decrease in C. difficile colonization in the waxworms.

The fact that this was an experimental lab study in waxworms means that conclusions can be made about cause and effect in this species.

Phages have not been used in humans to treat CDI and to see whether these results apply to people, an experimental trial with people would be necessary. However, work with insect models is crucial to our understanding of how best to exploit them. They have shown that these new models are useful tools in which to investigate the timings and dose regimens of phage treatment.

The paper is now published online and is expected to be published in a hard copy special issue of Frontiers in Microbiology.

The study was funded by AmpliPhi Biosciences Corporation, a developer of bacteriophage-based antibacterial therapies to treat drug-resistant infections.

Professor Martha Clokie has been investigating an alternative approach to antibiotics, which utilises naturally occurring viruses called bacteriophages, meaning ‘eaters of bacteria’, for nearly a decade at Leicester.

She said: “The results suggest that it may be possible to reduce the threat of C. difficile, and potentially other bacterial infections, through the use of phages both prophylactically to prevent infection, and as therapy once an infection is established. Phage therapy targets specific pathogenic bacterial populations while sparing patients’ beneficial microbiome.”

M. Scott Salka, CEO of AmpliPhi Biosciences, said: “The data support our products’ great potential in addressing antibiotic resistant and difficult to treat infections, including C. difficile. I would like to commend Dr. Nale and Professor Clokie for their exciting and insightful research demonstrating the immense promise of phage therapeutics. Their findings underscore our enthusiasm for the potential of our proprietary platform to enable the development of therapeutics to treat a broad range of bacterial infections that are resistant or have suboptimal responses to current antibiotic therapies.”

 

Source:

http://journal.frontiersin.org/article/10.3389/fmicb.2016.01383/full

 

Researchers At University of Texas Health Science Center and Graduate School of Biomedical Sciences in Houston Have Uncovered How C. difficile Produces the Toxins A and B That Are Responsible For Causing Disease

laboratorybeakers3

In the battle against drug-resistant pathogens, genetic research holds promising answers to our toughest threats. A new study shows that the best tool for
treating Clostridium difficile
infections could be within the genome of the bacteria itself.

Researchers at the University of Texas Health Science Center and the Graduate School of Biomedical Sciences in Houston have uncovered an important new finding to learn just how the C. difficile bacteria produces toxins, offering some new direction for the development of non-antibiotic drugs to fight dangerous C. difficile infections (CDI).

Strain on already stressed healthcare industry —–   The bacteria are one of the more virulent and widespread drug-resistant pathogens responsible for healthcare associated infections around the world, costing acute care facilities nearly $4.8 billion dollars a year in excess healthcare costs in the United States.

HOW is C. diff. Acquired?   —-   CDIs are linked to the use of broad spectrum antibiotics, which when used to treat infections can also suppress the beneficial bacteria that live in our guts and protect us from infections.   When that intestinal microflora is compromised, individuals become more susceptible to CDIs when exposed to C. difficile bacteria on contaminated surfaces or other individuals who are carrying the bacteria.

CDC Report —    C. difficile works by producing two toxins, toxin A and toxin B, that cause life-threatening diarrhea as well as pseudomembranous colitis, toxic megacolon, perforations in the colon, sepsis and — death. According to a 2015 study from the Centers for Disease Control and Prevention (CDC), there are nearly half a million CDIs in the United States each year, and about 15,000 of those cases result in deaths. The CDC considers C. difficile a public threat needing urgent and aggressive action.

The authors of the new study from the University of Texas have uncovered just how                 C. difficile produces the toxins A and B that are responsible for causing disease.

They studied several strains of the bacteria and found that some encode two Agr loci in their genomes, designated agr1 and agr2. The agr1 locus is present in all of the C. difficile strains sequenced to date, whereas the agr2 locus is present in a few strains.

Until recently, the function of these loci were not known. To understand their roles in toxin regulation and pathogenesis, the researchers used allelic exchange to delete components of agr1 and agr2 and then examined the mutants for toxin production. In their results, they found that the agr1 mutant cannot produce toxins A and B – in their model the mutant was able to colonize but could not produce disease.

These findings offer a potential new approach to treating CDIs for a global medical community vexed by the dangerous pathogen and in need of a novel solution.

“The toxins have become promising non-antibiotic treatment targets,” write the authors. “Here, we have identified a pathway responsible for activating the production of the toxins.

This important finding opens up a unique therapeutic target for the development of a novel non-antibiotic therapy for C. difficile infections.”

Study author Charles Darkoh, PhD, explains how his team plans on building on their research findings. “By crippling their toxin-making machinery, C. diff cannot make toxins and thus cannot cause disease. My laboratory is already working on this and was awarded a 5-year National Institutes of Health grant to investigate and develop an oral compound we have identified that inactivate the toxins and block the toxin-making machinery
of C. diff by targeting this pathway.”

To read article in its entirety click on the link below:

Researchers at MGGen Are Part Of a Community Study In Flagstaff, AZ On Two Serious Infection-Causing Bacteria; Clostridium difficile and Staphylococcus aureus

RESEARCH

RESEARCH

Researchers at Northern Arizona University’s Center for Microbial Genetics and Genomics, or MGGen, are putting out a call for poop.

The request is part of a community study on two nasty infection-causing bacteria in order to identify how the bugs are being carried around Flagstaff,  AZ and how they are making their way into the hospital.

The researchers say the pathogens could be present on any number of things, from dogs to ground meat to humans themselves.

It is hoped that confirming those reservoirs and tracking how the bacteria are transmitted will lead to new recommendations for how people and hospitals can better prevent the infections, the researchers said.

DNA MAPPING

The two bacteria, Clostridium difficile, or C. diff, and Staphylococcus aureus, or Staph, are important to study because they are notorious for causing hospital-acquired infections that are often difficult to treat.

Staph can cause skin and respiratory infections while symptoms of C. diff infections include diarrhea and fever.

For the research project, MGGen scientists are comparing Staph and C. diff bacteria collected from sick patients at Flagstaff Medical Center to those bacteria carried by healthy people.

Samples of the latter come from volunteers willing to provide a swab from inside their nose and a swab of their fecal material from used toilet tissue. The researchers have received 65 healthy community member samples and their goal is to get 500 by next April.

MGGen’s specialty is whole genome sequencing, which allows scientists to compare even the tiniest genetic variations between the samples. With that, they can tell how closely the samples are related, indicating potential transmission paths.

The study has found:  that the bacteria strains in ill patients don’t match those found in other hospital cases, indicating the organisms aren’t lingering in the hospital and being transmitted from patient to patient but are being acquired by people before they get into the hospital, said Heidie Hornstra O’Neill, research project coordinator at MGGen.

both bacteria species can live on and in healthy people without causing any problems, one possibility is that the pathogen hangs out in people’s bodies without causing any symptoms and then proliferates when the immune systems is weakened.

It could also be that only certain strains of the bacteria cause disease while others do not. About a third of people carry Staph bacteria, for example, but only a small percentage of people get a Staph infection, which could mean only some strains are dangerous, said Paul Keim, lab director at MGGen.

The researchers are collecting demographic information as well to see if a person’s gender, ethnicity or access to healthcare plays a role in whether they carry the bacteria.

SIDEWALK SCANNING

DOG POO SAMPLES:   Another potential source of C. diff bacteria, especially in a place like Flagstaff, is dogs, said Nate Stone, a research specialist at MGGen. Stone searched the sidewalks of Flagstaff for four months in the fall of 2014, collecting samples of dog poop to test them for C. diff. He found the bacteria were present in 17 percent of the 200 samples and half of the strains found are common in human C. diff infections. 

“We don’t know if dogs are giving humans C. diff or humans are giving dogs C. diff, but we do know dogs are carrying C. diff strains that can cause infections in humans, so they are probably one part of the story,” Stone said.

Next up, he’ll use genetic analysis to see if any bacteria from the dog poop samples match human samples, suggesting direct transmission.

Another possible C. diff reservoir is meat, and that’s also on Stone’s future research agenda.

The end goal of providing more data on these infection-causing bacteria is to help everyone from ordinary citizens to medical organizations figure out better ways to prevent them, Stone and Keim said.

“The reservoir stuff is fascinating because we think we can affect the way people live,” Keim said.

 

To read article in its entirety:

http://azdailysun.com/news/local/nau-researchers-track-path-of-infection-causing-bugs/article_3c0e8bc9-b432-5e6d-988e-53eee1e47bd4.html